P396: FIFTEEN YEARS OF RUSSIAN RESEARCH IN THE TREATMENT OF ADULT PATIENTS WITH ACUTE PH-NEGATIVE LYMPHOBLASTIC LEUKEMIA ACCORDING TO THE PROTOCOLS ALL-2009 AND ALL-2016.
Authors: Olga Aleshina (Gavrilina), Vera Troitskaya, Irina Galtseva, Ekaterina Kotova, Galina Isinova, Yulia Chabaeva, Zalina Akhmerzaeva, Sergey Bondarenko, Olga Baranova, Maria Grishunina, Olga Samoilova, Kamil Kaplanov, Tatiana Konstantinova, Yulia Sveshnikova, Elena Borisenkova, Natalia Minaeva, Elena Zinina, Valeriy Lapin, Andrey Sokolov, Sergey Kulikov, Alina Antipova, Valentina Dvirnyk, Andrey Sudarikov, Tatiana Obukhova, Elena Parovichnikova
Journal: HemaSphere (2023)

Background: Beginning in April 2009 the Russian Research Group for the Study of Ph-negative ALL in Adults conducted multicenter studies ALL-2009(NCT01193933) and ALL-2016(NCT03462095) based on a de-escalated but non-interruptive treatment approach with low numbers of allo-HSCT. The ALL-2009 study provided the cornerstone for further de-escalation of the consolidation phase in a new RALL-2016 study with centralized MRD-monitoring. Aims: To compare long-term (5-year) results of two studies and detect the factors of unfavorable prognosis for adult patients with Ph-negative ALL. Methods: The studies were performed from Apr 2009 to Dec 2016 (ALL-2009) and from Dec 2016 till to Jan 2023 (ALL-2016), with 642 patients included: 330 in ALL-2009 and 312 in ALL -2016. The analysis was completed in Jan 2023. The median age of patients in ALL-2009 was 28 years (15-55), ALL-2016 - 32.5 years (18-55), f/m 147/182 were recruited in ALL-2009 and 117/195 – in ALL-2016. In the ALL-2009 protocol the 6-pts phenotype was unknown. Biphenotypic AL was diagnosed in – 1,2% (n=4), T-ALL/lymphoma – in 38,7% (n=125), and BCP-ALL - in 59,1% (n=194) of the enrolled patients. In the ALL-2016 protocol biphenotypic AL was diagnosed in – 4% (n=13), T-ALL/lymphoma – in 39% (n=123), and BCP-ALL - in 57% (n=176) of patients. Cytogenetic studies were performed in 242 patients in ALL-2009 (73.3%) and 287 patients in ALL-2016 (92%). Patients in the ALL-2016 protocol underwent a centralized assessment of minimal residual disease (MRD) by flow cytometry on protocol day +70 (after completion of two induction phases), +133 and +190 days. Transplantation of allogeneic stem hematopoietic cells was performed in 7% of patients in ALL-2009 and 9% in ALL-2016. Results: The 5 year overall, disease-free survival (OS, DFS) and the probability of relapse were 59%, 63%, 23% for ALL-2009 patients, and for ALL- 2016 patients - 67%, 59%, 22%, respectively. For patients with B-cell precursor ALL, two cytogenetic risk groups were formed, in which long-term survival rates significantly differed: the standard group (hyperploid set of chromosomes and normal karyotype) - OS 63%, RFS 70% - and high cytogenetic risk (any abnormal karyotype, except for hyperploidy) - OS 49%, DFS 52% (p=0.001, p=0.0014). In T-ALL, cytogenetic markers had no prognostic value, but the immunophenotype of ETP T-ALL turned out to be an important predictor of poor prognosis (the probability of relapse was 52% compared with 15% for all other immunophenotypic variants). According to the results of centralized monitoring of MRD, it was determined that for B-cell precursor ALL, the significant negative factors were the high cytogenetic risk group and positive MRD status at +70 days, and for T-cells, the early immunophenotype and positive MRD status at +133 days. Summary/Conclusion: The results of the ALL-2009 and ALL-2016 studies show that the effectiveness of the two Russian protocols is absolutely the same and MRD persistence after induction is the main factor for poor prognosis for Ph-negative ALL.Keywords: Adult, Multicenter, Chemotherapy, Acute lymphoblastic leukemia